Biology subjects

Jamil, N.

Publications and source records attributed to Jamil, N..

3 recordsLinked to original sources

bioRxiv2026

Recurrent Escape from Osimertinib-Induced Senescence Promotes Genomic Instability Associated with Therapeutic Resistance

Acquired resistance to osimertinib remains a major challenge in treating EGFR-mutant (EGFR+) Non-Small-Cell Lung Cancer (NSCLC). Although most patients initially respond to treatment, relapses are universal, even after prolonged remission during which tumor dormancy occurs. Here, we show that osimertinib induces and maintains senescence in EGFR+ NSCLC. Importantly, osimertinib does not kill senescent cells; however, following drug withdrawal, cells escape and resume proliferation. To examine the consequences of recurrent senescence and escape on resistance, we generated four isogenic cell lines clonally expanded through sequential cycles of Osimertinib-Induced Senescence (OsIS). Phylogenetic reconstruction based on de novo somatic variants revealed that these lines form four distinct evolutionary clades with varying degrees of osimertinib resistance. All had elevated tumor mutational burden with distinct single-nucleotide and copy-number variants, and without acquisition of tertiary EGFR mutations or MET amplification. Resistance was predominately associated with chromosomal instability characterized by extensive loss of heterozygosity, high copy-number alteration burden, and mutational signatures consistent with replication-associated DNA damage and repair. A second resistance genotype exhibited extreme focal amplifications with breakage-fusion-bridge-like genome remodeling. Despite profound genomic instability, targeting DNA repair or replication stress pathways was ineffective, whereas sensitivity to platinum-based chemotherapy was retained across clades. Collectively, these findings indicate that recurrent senescence escape drives osimertinib resistance through widespread genomic instability and is most effectively treated by cytotoxic strategies rather than pathway-targeted approaches. SignificanceAlthough most patients with EGFR+ lung cancer relapse after osimertinib therapy, only a small fraction of cases are explained by on-target resistance mutations. This study shows that recurrent cycles of osimertinib-induced senescence and escape promote resistance through chromosomal instability, identifying dormant cells as critical reservoirs for relapse. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/704600v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@6e2b66org.highwire.dtl.DTLVardef@e337cforg.highwire.dtl.DTLVardef@16526adorg.highwire.dtl.DTLVardef@1ce4d80_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Detection of Echinococcus spp. and other taeniid species in lettuces and berries: two international multicenter studies from the MEmE project

Cystic and alveolar echinococcosis are severe zoonotic diseases characterized by long asymptomatic periods lasting months or years. Viable Echinococcus eggs released into the environment through the feces of canids can infect humans through accidental ingestion via hand-to-mouth contact or consumption of contaminated food or water. Both Echinococcus multilocularis and Echinococcus granulosus sensu lato are considered as foodborne parasites. However, when considering possible pathways of human infection, it appears that food and water-borne related variables do not significantly increase the risk of infection. Providing evidence-based data for the presence of DNA and, potentially, eggs in fresh produce is crucial in understanding foodborne transmission of Echinococcus spp. to humans. Two multicenter and multicountry studies were conducted within the One Health EJP framework to estimate the proportion of lettuces and berries contaminated by E. multilocularis, E. granulosus s.l., and other taeniid DNAs from 12 European countries, Tunisia and Pakistan. A total of 1,117 lettuces, 300 strawberries and 130 blueberries samples were collected and analyzed by washing, sequential sieving and real-time PCRs. Echinococcus multilocularis DNA was detected in 1.2% (7/570) of samples tested from the seven European endemic areas and in 2% (2/100) from Pakistan. In the five European endemic countries for E. granulosus s.l., E. granulosus sensu stricto DNA was identified in 1.3% of lettuces (9/695). The proportion of lettuces contaminated by E. granulosus sensu stricto DNA was 12% (9/75) in Tunisia and 4% (4/100) in Pakistan. Regarding berries, E. multilocularis DNA was detected in 5.4% of strawberries (n=11/202), 7.3% of blueberries (6/82) from the seven European endemic countries and 56% of blueberries (14/25) from Pakistan. High contamination rates of E. granulosus s.s were found outside of Europe, with 12.0% in blueberries (3/25) from Pakistan and 81.3%. DNA in strawberries (13/16) from Tunisia. The total contamination rate of all taeniid species DNA in lettuces (5.3%; 59/1,117) and berries (12.1%; 58/480) suggests that the transfer of taeniid eggs from carnivore feces to food is not uncommon. Although we assume that eggs are the source of the DNA detected in this study, the viability of such eggs is unknown. The detection of Echinococcus species in lettuces and berries suggests a potential risk of foodborne human infection. The relative contribution of this risk remains to be estimated. Further studies on food and environmental contamination are necessary to cover different epidemiological contexts and social habits, leading to a better understanding of human infections by Echinococcus eggs.

microbiology↗

bioRxiv2019

Factors Affecting Detection Of GMO Traces In Food And Crop Samples

Rice is one of the highly consumable and demanded food crops throughout the world. To meet this requirement, genetically modified (GM) crops were introduced, which were met with sturdy and frequently angry opposition by the user. To handle the situation labeling of GM food / crop was advised, thus demand for traceability and detection of unknown modified genes increased. Modified genes are detected by various methods; these methods are affected by several factors as reported in international standards. Those factors include presence / absence of shells, husk, and dust, method of DNA extraction and different PCR primers. These factors ultimately pose hindrance in detection of modified genes. This study was conducted to analyze the effects of the above mentioned factors on detection of GM rice samples. Furthermore two different sets of primers were used with same samples and their impact on the PCR detection was observed. The results showed a significant difference in DNA concentration between the rice samples with husk, without husk and after seed germination. Furthermore, the change of PCR primer set also affected the detection of genetic modifications. This allows analysis of the potential factors that may have impact on the final results.

plant biology↗